The overall objective of this project is to provide an understanding of the mechanisms and the extent to which various fetal systems can maintain adequate function in the presence of varying degrees of reduction in supply of oxygen and nutrients. In our current research we have developed a model for mild intrauterine growth retardation (IUGR) in the sheep. Despite the presence of elevated catecholamines and significant chronic hypoxemia and hypoglycemia, the renal and cardiovascular functions of these fetuses are not different from normal fetuses. To test the hypothesis that mild IUGR is associated with adaptation while additional stress or more severe IUGR leads to compromise, we will investigate the consequences of both mild and severe hypoxia on several functions. Our specific aims are: 1`. To develop a model of severe IUGR, chronic fetal hypoxemia and hypoglycemia in th e sheep through the induction of pronounced maternal hypovolemia. 2. To study adaptation of the following functions in the mildly and severely growth restricted fetuses through exposure to three acute conditions; i) episodes of hypoxia, ii) restoration of oxygen levels to normoxemia, and iii) restoration of glucose levels to euglycemia: (a) The role and interaction of fetal catecholamines, prostaglandins and insulin, (b) Fetal renal function, maintenance of fetal vascular volume, and volume and composition of amniotic fluid, (c) The regulation of fetal heart rate and blood pressure, (d) The regulation of fetal breathing and the organization of behavioral states. In addition our Collaborative Aims are; 3. To test hypotheses that increases in the ratio of tryptophan to other large neutral amino acids in fetal plasma increases CNS serotonin activity and alters indices of bother central and peripheral nervous system activity' these effects are blocked by tyrosine and accentuated by acute and chronic hypoxia (Schulze). 4. To establish a model for chronic hypoxia and intrauterine growth restriction in the fetal baboon using the techniques developed in the pregnant sheep for prevention of the normal expansion of maternal blood volume ((Stark). These studies will define the extent of adaptation and the nature of the compromise. This will lead to a better understanding of problems related to intrauterine growth retardation, a significant factor in neonatal mortality and morbidity as well as in the sudden infant death syndrome.